Genome-Wide Association Study of Telomere Length Among South Asians Identifies a Second RTEL1 Association Signal

Details

• Personal Author:
  Ahmed A ; Ahsan H ; Argos M ; Chen LS ; Delgado DA ; Gao J ; Islam T ; Jasmine F ; Kibriya MG ; Pierce BL ; Rahman M ; Rakibuz-Zaman M ; Roy S ; Sabarinathan M ; Sarwar G ; Shahriar H ; Shinkle J ; Tong L ; Yunus M ; Zhang C
• Description:
  Background: Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report approximately 10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry. Objective: This study aims to enhance our understanding of genetic determinants of TL across populations. Methods: We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes. Results: Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10-8 and P=6.4×10-6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10-7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (=0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only. Conclusions: In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus. [Description provided by NIOSH]
• Subjects:
  Biological Assay Biomarkers Blood Enzymes Genetics Hematologic Tests Nucleotides Occupational Health Race Factors Safety
• Keywords:
  Bioassays Blood Samples Deoxyribonucleic Acids DNA Enzyme Complexes Genes Genetic Predisposition Genomics Genotype Heredity Humans Leukocytes Molecular Biology Molecular Signaling Racial Factors Ribonucleic Acids RNA

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• ISSN:
  0022-2593
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Georgia ; Illinois ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  64-71
• Volume:
  55
• Issue:
  1
• NIOSHTIC Number:
  nn:20051403
• Citation:
  J Med Genet 2018 Jan; 55(1):64-71
• Contact Point Address:
  Dr Brandon L Pierce, Department of Public Health Sciences, The University of Chicago, 5841 South Maryland Avenue, MC2000 Chicago, IL 60637, USA
• Email:
  brandonpierce@uchicago.edu
• Federal Fiscal Year:
  2018
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Journal of Medical Genetics
• End Date:
  20290630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:501682358b19fcb5f78db4b53288a81adb674c37b6f9c7179b47530b0d26e33e9517c339d00e24b5d0c42d0ad42e09c29c06b398a52e18f3ceac6f8a235f6fab
• Download URL:
  https://stacks.cdc.gov/view/cdc/211374/cdc_211374_DS1.pdf
• File Type:
  [PDF - 862.53 KB ]